A dose-response study of growth hormone (GH) replacement on whole body protein and lipid kinetics in GH-deficient adults.
This study was designed to establish the lower dose of effective GH replacement therapy in severe GH-deficient (GHD) adults. Whole body protein and lipid kinetics were determined in six GHD men in the basal state (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) micrograms/kg.day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-13C]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg.h); those of lipolysis (measured in four of the six patients) were estimated by infusing [1,1,2,3,3-D5]glycerol (prime, 1.8 mumol/kg; infusion rate, 0.06 mumol/kg.min). Serum insulin-like growth factor I (IGF-I) concentrations (picograms per mL; mean +/- SE) similarly increased from the basal level (39 +/- 7) after 3.3 (108 +/- 18) or 2 (109 +/- 24) microgram/kg.day rhGH (P < 0.001 vs. basal), whereas they did not change with placebo (41 +/- 8). Leucine Ra was unaffected by the treatments. GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect. In conclusion, 1) at least 3.3 micrograms/ kg.day rhGH are required to increase whole body protein synthesis and lipolysis in male GHD adults; 2) 2 micrograms/kg.day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also effective on intermediate metabolism.
Lucidi
P
P
Department of Internal Medicine, Endocrine and Metabolic Sciences, University of Perugia, Italy.
Lauteri
M
M
Laureti
S
S
Celleno
R
R
Santoni
S
S
Volpi
E
E
Angeletti
G
G
Santeusanio
F
F
De Feo
P
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002247:Carbon Isotopes; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007651:Keto Acids / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000097:blood; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use
D001786:Blood Glucose; D002096:C-Peptide; D002247:Carbon Isotopes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007651:Keto Acids; D011506:Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005990:Glycerol